Conditional inactivation of SREBP cleavage-activating protein (SCAP) in oligodendrocytes reduces lipogenic gene expression and causes motor control defects and reduced survival.

<p><b>A)</b> Protein levels of precursor sterol regulatory element-binding protein 2 (SREBP2) and mature (processed) SREBP2 were determined by immunoblotting of total extracts of the spinal cord of wild-type (WT) and CNP-SCAP animals at P20 (<i>n</i> = 3). Detection of mature and precursor SREBP2 was performed using different exposure times, and representative pictures are shown. Detection of beta-actin and on-blot protein stain was used to control for equal loading. <b>B)</b> Histogram shows quantification of precursor and mature SREBP2 protein levels after correction for equal loading (using on-blot stain) and subsequent normalization to WT levels in which the WT levels were set to 1, and the ratio between mature/precursor SREBP in which the ratio for WT was set to 1. All data are presented as mean levels ± SEM (<i>t</i> test: *<i>p</i> < 0.05, #<i>p</i> = 0.059). <b>C)</b> Expression of fatty acid synthase (FASN, green) in oligodendrocytes (Olig2, blue) and astrocytes (glial fibrillary acidic protein [GFAP], red) of WT or CNP-SCAP mutant mice at P20. Asterisks denote oligodendrocytes with FASN expression; arrowheads denote astrocytes with FASN expression (scale bar, 25 μm). <b>D)</b> Number of FASN-positive oligodendrocytes (Olig2⁺FASN⁺) and FASN-positive astrocytes (GFAP⁺FASN⁺) in WT and CNP-SCAP mice (<i>n</i> = 3). The values are provided as the percentage of the total number of oligodendrocytes (Olig2+ cells) or astrocytes (GFAP⁺ cells). Data are presented as mean ± SEM. **<i>p</i> < 0.01 using <i>t</i> test. <b>E)</b> Kaplan-Meier survival plot showing a strongly reduced life span of CNP-SCAP mice compared to age-matched WT mice. <b>F)</b> Body weight development of WT and CNP-SCAP mice over a 3-month period. Shown are the mean and SEM. <b>G)</b> At a grid test, CNP-SCAP mice showed limb ataxia, causing frequent slips of the hind limbs (red arrow) or front limbs. Mutant mice showed an abnormal reaction when tail lifted; they attempted to clasp their hind limbs and clench the toes of their rear feet. <b>H)</b> CNP-SCAP brains compared to control littermates at P28. The numeric data underlying Fig 1B, D, E and F can be found in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002605#pbio.1002605.s006" target="_blank">S1 Data</a>.